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Cameron S. Cowan, JiJie Pang, Samuel Wu; Comparison Of DBA2/J Intraocular Pressure Histories With Physiological, Morphological, And Behavioral Measures Of Retinal Function And Degeneration. Invest. Ophthalmol. Vis. Sci. 2011;52(14):707.
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© ARVO (1962-2015); The Authors (2016-present)
This project utilizes the DBA2/J mouse strain, which is considered a glaucoma model because it has an intraocular pressure (IOP) increase and retinal ganglion cell (RGC) death starting at 7 months. RGC death is a focal point of glaucoma, however the loss of function in RGCs prior to cell death is poorly characterized. Since understanding that dysfunction could have diagnostic utility, this project attempts to characterize it by recording RGC light responses. That data is combined with behavioral and anatomical information, and compared to IOP histories on an eye by eye basis. This approach addresses important concerns regarding the connection between RGC death and IOP in these mice.
IOP was measured with a rebound tonometer, with at least 3 measurements taken at ~10 day intervals after mice reached 3 months of age. Groups of mice were then sacrificed at three month intervals, starting at 4 months. Before sacrifice, their optokinetic reflex threshold, a behavioral metric of visual acuity, was determined for both eyes. To characterize RGC function, retinas either had their RGC light responses recorded with a multielectrode array or, to assay degeneration, RGC cell bodies were back-filled with dye via the optic nerve.
After mice reach their 7th month, ~%50 of IOP recordings rise from normal (~12 mmHg) to elevated (>25 mmHg) levels. While ~30% of IOPs remain high after elevating, ~%20 return to normal levels. In preliminary findings, at 6 months ~21% of mouse RGCs fire action potentials spontaneously but lack light evoked responses, compared to <5% in 3 month old DBA2/J mice. ON and OFF RGCs from the 6 month old mice also required brighter light levels, on average, to reach both their firing threshold and their half maximal firing rate. Anatomical results confirmed previous findings that showed RGC death starting at 8 months.
RGC death was present after 8 months of age, and levels were consistent with past results. Results thus far suggest that light responses of DBA2/J RGCs, in particular their light sensitivity, are dysfunctional prior to IOP increase. The observed IOP variation with time highlights the difficulty of correlating previous RGC morphology results with single IOP measurements. We are investigating whether IOP trends, peak amplitudes, or cumulative IOP over months are significantly correlated with RGC death and dysfunction.
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